Abstract
Eukaryotic cells possess overlapping mechanisms to ensure that DNA replication is restricted to the S phase of the cell cycle. The levels of hOrc1p, the largest subunit of the human origin recognition complex, vary during the cell division cycle. In rapidly proliferating cells, hOrc1p is expressed and targeted to chromatin as cells exit mitosis and prereplicative complexes are formed. Later, as cyclin A accumulates and cells enter S phase, hOrc1p is ubiquitinated on chromatin and then degraded. hOrc1p destruction occurs through the proteasome and is signaled in part by the SCF(Skp2) ubiquitin-ligase complex. Other hORC subunits are stable throughout the cell cycle. The regulation of hOrc1p may be an important mechanism in maintaining the ploidy in human cells.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Cell Cycle / physiology*
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / metabolism
-
Cell Fractionation
-
Chromatin / metabolism*
-
Cyclin A / metabolism
-
Cysteine Endopeptidases / metabolism
-
DNA Damage
-
DNA Replication / physiology*
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Flow Cytometry
-
Gene Silencing
-
HeLa Cells
-
Humans
-
Macromolecular Substances
-
Multienzyme Complexes / metabolism
-
Origin Recognition Complex
-
Phosphorylation
-
Proteasome Endopeptidase Complex
-
Protein Subunits
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
S-Phase Kinase-Associated Proteins
-
Ubiquitin / metabolism*
Substances
-
Cell Cycle Proteins
-
Chromatin
-
Cyclin A
-
DNA-Binding Proteins
-
Macromolecular Substances
-
Multienzyme Complexes
-
ORC1 protein, human
-
Origin Recognition Complex
-
Protein Subunits
-
Recombinant Fusion Proteins
-
S-Phase Kinase-Associated Proteins
-
Ubiquitin
-
Cysteine Endopeptidases
-
Proteasome Endopeptidase Complex